Objective: To investigate the effect of controlled mechanical ventilation (CMV) on the diaphragm of rats, and therefore to understand the theoretic basis of difficulty weaning due to dysfunction and morphology in diaphragm induced by inappropriate mechanical ventilation.
Methods: Twenty-four adult male SD rats were randomly assigned into 3 experimental groups: a control group, a 18 h CMV group, and a 24 h CMV group. Trans-diaphragmatic pressure (Pdi), maximal trans-diaphragmatic pressure (Pdimax), diaphragm electromyogram (EMGdi), and diaphragm muscle force were measured during CMV at various stimulation frequencies. Morphological changes of the diaphragm myofibril were observed by transmission electron microscopy. Myosin heavy chain (MHC) isoform expression were analyzed with SDS-glycerol PAGE and Western blotting.
Results: The Pdimax in the 18 h CMV group and the 24 h CMV group [(8.98+/-0.55, 6.12+/-0.53) cm H2O, 1 cm H2O=0.098 kPa] was significantly reduced (F=82.35, P<0.01) compared with the control group [(14.92+/-0.16) cm H2O]. The Fc and the H/L decreased significantly. At the stimulation frequency of 100 Hz, the diaphragm muscle force in the 18 h CMV group and 24 h CMV group [(84.11+/-0.43) N, (52.65+/-0.64) N, respectively] decreased compare with the control [(98.13+/-0.50) N, F=15.02, P<0.01]. The proportion of MHC2A decreased in the 24 h group compared with control. The ultrastructural changes of the diaphragm was observed in the 24 h CMV group, such as disrupted myofibrils, increased numbers of lipid vacuoles in the sarcoplasm, and abnormally small mitochondria containing focal membrane disruptions.
Conclusion: Short-term CMV induced diaphragm fatigue and altered the function and morphology of diaphragm in SD rats. Diaphragmatic dysfunction induced by CMV maybe one of the important reasons for difficult weaning.